Clinicopathological Characterization of Digital Papillary Adenocarcinoma With Emphasis on Low-risk Human Papillomavirus In Situ Hybridization and BRAF-VE1 Immunohistochemistry.

Digital papillary adenocarcinoma (DPA) is a rare malignant sweat gland tumor affecting fingers and toes most commonly. Human papillomavirus type 42 (HPV42), a low-risk HPV type, is an important diagnostic criterion. No uniform mutational signature has been detected in DPA except for BRAF mutations encoding p.V600E in small case series and in single case reports. The aim of this study was to add to the data on the prevalence of low-risk HPV/HPV42 detection and BRAF-VE1 immunohistochemistry in digital papillary adenocarcinoma. H and E-stained sections and immunohistochemistry for S100, SOX10, SMA, p63/p40, CK7, CK5/6, YAP1, and BRAF-VE1 were reviewed, and in situ hybridization (ISH) for low-risk HPV (including HPV42) or specifically HPV42 was performed. Clinical follow-up was obtained from patient records. Twenty-eight tumors were included and presented on the fingers (23), feet (4), and vulva (1) with a median size of 1.5 cm. The patient age ranged from 11 to 88 years (median: 49.5; M:F=6:1). Histopathologically, digital papillary adenocarcinomas presented as multinodular, poorly- or well-circumscribed tumors in the dermis and subcutaneous tissue, with solid, cystic, and papillary growth patterns. Cytologic atypia was mild to moderate. All tumors were positive for low-risk HPV and/or HPV42. BRAF-VE1 immunohistochemistry was negative in all tumors. Two patients developed distant metastases; all other patients were alive without recurrence (median follow-up: 46.5 mo, range: 5 to 192 mo). In conclusion, this study does not support the pathogenic role of BRAF p.V600E in digital papillary adenocarcinoma but confirms low-risk HPV/HPV42 infection as the only driver in all tumors.